CoreA:Imaging,ProteinProduction,andChemicalBiologyCore SUMMARY/ABSTRACT ThegoaloftheImaging,ProteinProduction,andChemicalBiologyCoreistomaximizethescientificprogress andproductivityofPPGinvestigatorsbyprovidingessentialservicesandreagents.Thecorewillperformthree major functions for the PPG: (1) advanced light and electron microscopy imaging;? (2) protein and antibody production;?and(3)chemicalproteomics.AllthreePPGcomponentprojectswillutilizeatleasttwocoreservices, and two of the projects will utilize all three. Centralizing these activities within a core will benefit the PPG by increasingproductivityandreducingcosts.Thecorewillprovidefull-servicescanningandtransmissionelectron microscopy, standard and live-cell confocal fluorescence microscopy, and NanoSIMS imaging. The latter is a massspectrometry?basedimagingmodalitythatmakesitpossibletocreatehigh-resolutionimagesofcellsand tissuesbasedsolelyontheirisotopiccontent.PPGinvestigatorswilluseNanoSIMStovisualizeandquantifythe localization and movement of lipids in cells and tissues. PPG investigators will also study new molecules and novel mechanisms regulating lipid transport and signaling, for which few reagents exist. To assist these investigations, the core will produce protein and antibody reagents for PPG studies (e.g., soluble GPIHBP1, stable isotope?labeled ALO-D4, 5D2 Fab fragments). Finally, the core will perform Activity-Based Chemical ProteomicsandisotopicTandemOrthogonalProteolysis?Activity-BasedProteinProfiling.Thesestate-of-the-art proteomics discovery platforms will be used to identify proteins involved in the intracellular trafficking of HDL- derived cholesterol and the regulation of STING signaling by cholesterol.For the next five years, the core is poised?with the experience, robust protocols, and experienced personnel?to provide vital services to PPG investigators.